The effect of Vitamin D Consumption and High‑Intensity Interval Training on the Expression of Long Non‑Coding RNA miR‑۹ in the Hippocampus of Adult Male C۵۷ Mice Fed a High‑Fat Diet

High‑fat diet (HFD) induces metabolic and neurobiological alterations that negatively affect the hippocampus, a brain region critical for learning and memory. Evidence suggests that these effects are partly mediated by dysregulation of microRNAs, particularly miR‑۹, which regulates neuronal differentiation, synaptic plasticity, and neuroinflammatory signaling. Elevated miR‑۹ expression under HFD conditions has been associated with oxidative stress, activation of inflammatory pathways, and impaired neuronal homeostasis. Interventions such as physical exercise and vitamin D supplementation may counteract these molecular disturbances through anti‑inflammatory, neurotrophic, and epigenetic mechanisms. This study examined the independent and combined effects of high‑intensity interval training (HIIT) and vitamin D supplementation on hippocampal miR‑۹ expression in adult male C۵۷BL/۶ mice fed an HFD. Twenty mice were randomly assigned to four groups (n=۵): HFD, HIIT+HFD, HIIT+HFD+VitD, and HIIT+HFD+DMSO. The intervention lasted six weeks. Following a one‑week familiarization period, mice in the training groups performed a progressive HIIT protocol consisting of repeated high‑intensity running bouts with active recovery intervals. The HIIT+HFD+VitD group received daily intraperitoneal vitamin D (۵ μg/kg) after exercise, whereas the HIIT+HFD+DMSO group received the vehicle (DMSO). Hippocampal tissues were collected ۴۸ hours after the final training session. Data were analyzed using one‑way ANOVA followed by LSD post‑hoc testing (P ≤ ۰.۰۵). Significant differences in miR‑۹ expression were observed among groups. The HIIT+HFD+VitD group exhibited the lowest miR‑۹ levels, significantly lower than the HFD, HIIT+HFD, and HIIT+HFD+DMSO groups. Although HIIT alone reduced miR‑۹ expression compared with HFD, the combined intervention produced a greater effect, while DMSO showed no comparable influence. These findings indicate that HIIT attenuates HFD‑induced hippocampal miR‑۹ dysregulation and that vitamin D supplementation enhances this effect, potentially improving the molecular environment and neuroinflammatory status of the hippocampus.

کلیدواژه ها:

High‑fat diet ، High‑intensity interval training ، Vitamin D ، miR‑۹ ، Hippocampus ، Neuroinflammation